USE OF miRNA 148 CLUSTER AS MARKER FOR DIAGNOSING AND/OR TREATING COGNITIVE IMPAIRMENT-ASSOCIATED DISEASES

Abstract

The present disclosure discloses use of a miRNA 148 cluster as a marker for diagnosing and/or treating cognitive impairment-associated diseases. The present disclosure provides use of the miRNA 148 cluster in the diagnosis and treatment of cognitive impairment-associated diseases. The expression level of the miRNA 148 cluster is detected using primers for the microRNA through cognitive impairment-associated disease models, and it is found that the expression of the miRNA 148 cluster is significantly reduced during the progression of the cognitive impairment-associated diseases. The miRNA 148 cluster is found to directly target p35 to inhibit hyperphosphorylation of Tau and can be negatively regulated by the upregulated PTEN in AD pathology. Upregulation of miRNA 148 cluster improves the cognitive dysfunction and inhibit the hyperphosphorylation of Tau in AD pathology, in which the PTEN/Akt/CREB and p35/CDK signaling pathways play a key role.

What is claimed is: 
     
         1 . A product with an active ingredient of a miRNA 148 cluster or an expression promoter thereof, wherein, use of the product comprises the following (a), (b), (c) and/or (d):
 (a) inhibiting Tau phosphorylation;   (b) alleviating neurodegeneration and providing a neuroprotective effect;   (c) diagnosing and/or treating cognitive impairment-associated diseases; and   (d) reducing the expression of p35, p25, and CDK5.   
     
     
         2 . The product according to  claim 1 , wherein the miRNA 148 cluster or the expression promoter thereof is used in the following (a), (b), (c), and/or (d):
 (a) preparation of a substance that can inhibit phosphorylation of Tau;   (b) preparation of a substance that can alleviate neurodegeneration and has a neuroprotective effect;   (c) preparation of a substance for diagnosing and/or treating cognitive impairment-associated diseases; and   (d) preparation of a substance for reducing the expression of p35, p25, and cyclin-dependent kinase 5 (CDK5).   
     
     
         3 . The product according to  claim 1 , wherein,
 the miRNA 148 cluster is selected from hsa-miR-148a, with a nucleotide sequence shown in SEQ ID NO. 1; and   the miRNA148 cluster is selected from hsa-miR-148a-3p, with a nucleotide sequence shown in SEQ ID NO. 2.   
     
     
         4 . The product according to  claim 1 , wherein,
 the product for diagnosing cognitive impairment-associated diseases is a detection kit;   the detection kit comprises primers of the miRNA148 cluster; and the assay kit is used to diagnose cognitive impairment-associated diseases, predict the risk of developing cognitive impairment-associated diseases, or predict the outcome of cognitive impairment-associated diseases in patients suffering from or at risk of developing cognitive impairment-associated diseases.   
     
     
         5 . The product according to  claim 4 , wherein,
 the primer is used to determine an expression level of the miRNA 148 cluster in a sample.   
     
     
         6 . The product according to  claim 1 , wherein,
 the expression level of the miRNA 148 cluster is based on an expression level of the miRNA 148 cluster in a patient and a reference expression level of the miRNA 148 cluster in a healthy subject; and   if the expression level of the miRNA 148 cluster is significantly lower than the reference expression level of the miRNA 148 cluster in a healthy subject, it indicates that the patient has or is at risk of developing a cognitive impairment-associated disease.   
     
     
         7 . The product according to  claim 1 , wherein,
 the expression level of the miRNA 148 cluster is determined by a sequencing-based method, an array-based method, or a PCR-based method.   
     
     
         8 . The product according to  claim 1 , wherein,
 the expression promoter of the miRNA 148 cluster is at least one of a reagent, a medicament, a preparation, and a gene sequence that promotes the expression or activation of Akt, a reagent, a medicament, a preparation, and a gene sequence that promotes the expression or activation of cAMP-response element binding protein (CREB), and a reagent, a medicament, a preparation, and a gene sequence that inhibits the expression or activation of PTEN;   the Akt and CREB up-regulate the expression of the miRNA 148 cluster; and the PTEN down-regulates the expression of the miRNA 148 cluster.   
     
     
         9 . Use of an agonist for a miRNA 148 cluster in the preparation of a medicament for treating cognitive impairment-associated diseases. 
     
     
         10 . Use of a long non-coding RNA (lncRNA) interactive with a miRNA 148 cluster in the preparation of a medicament for treating cognitive impairment-associated diseases.